PF-07284892 in Participants With Advanced Solid Tumors

A PHASE 1, OPEN-LABEL, MULTI-CENTER, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PRELIMINARY EVIDENCE OF ANTI-TUMOR ACTIVITY OF PF-07284892 (ARRY-558) AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

The purpose of this first-in-patient, open label study is to determine the maximum tolerated dose and/or recommended dose for further study of PF-07284892 as a single agent and in combination with lorlatinib, encorafenib and cetuximab, or binimetinib and evaluate the pharmacokinetics, safety, and preliminary clinical activity of single agent and each combination therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: PF-07284892; Drug: lorlatinib; Biological: cetuximab; Drug: encorafenib; Drug: binimetinib

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic in Arizona - Phoenix
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • California
    • Encinitas, California, United States, 92024
      • California Cancer Associates for Research and Excellence
    • San Marcos, California, United States, 92069
      • California Cancer Associates for Research and Excellence
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Grand Rapids, Michigan, United States, 49546
      • Start Midwest
    • Novi, Michigan, United States, 48377
      • Henry Ford Medical Center - Columbus
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester, Minnesota
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center David H Koch Center for Cancer Care
    • New York, New York, United States, 10022
      • Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavilion
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology PLLC
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • SCRI Oncology Partners
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute- Pharmacy
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Md Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years at the time of informed consent
• Histological or cytological diagnosis of ALK-positive advanced NSCLC, CRC with BRAF V600E mutation, or RAS- mutant, NF1-mutant or BRAF class 3 mutant solid tumor. Participants with ROS-positive NSCLC are also eligible for Part 1 and 2 (Other ROS1-positive solid tumors may be considered after discussion with the sponsor).
• Documentation evidence of biomarker mutation status
• Part 3:

ALK-positive NSCLC with prior lorlatinib and no prior platinum-based chemotherapy (Cohort 1); with prior lorlatinib and prior platinum-based chemotherapy (Cohort 2); or with no prior lorlatinib (Cohort 3).

BRAF V600E mutant CRC participants resistant to BRAFi plus EGFRi (Cohort 4 ); refractory to BRAFi plus EGFRi (Cohort 5); or BRAFi plus EGFRi naïve (Cohort 6).

RAS- mutant, NF1-mutant or BRAF class 3 mutant solid tumors who have received prior SOC (Cohort 7).

Exclusion Criteria:

• Brain metastasis larger than 4 cm
• Active malignancy within 3 years
• Systemic anti-cancer therapy or small molecule therapeutics within 2 weeks prior to start of study treatment. Antibody based agents within 4 weeks prior to start of study treatment. Mitomycin C or nitrosoureas within 6 weeks prior to start of study treatment.
• For participants who may get lorlatinib or encorafenib on study, history of interstitial lung disease
• For participants who may get binimetinib on study, history or current evidence of retinal vein occlusion (RVO) or concurrent neuromuscular disorder associated with elevated creatine kinase (CK)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-07284892 monotherapy; Monotherapy dose escalation of PF-07284892 in participants with ALK- or ROS1-positive non-small cell lung cancer (NSCLC), B-type Raf proto-oncogene V600E mutation colorectal cancer (CRC), or RAS- mutant, NF1-mutant or BRAF class 3-mutant solid tumors	Drug: PF-07284892; PF-07284892; Other Names: ARRY-558
Experimental: PF-07284892 in combination with lorlatinib (Part 2); Combination dose escalation of PF-07284892 in combination with lorlatinib in participants with ALK- or ROS1-positive NSCLC	Drug: PF-07284892; PF-07284892; Other Names: ARRY-558; Drug: lorlatinib; lorlatinib; Other Names: Lorbrena; PF-06463922, Lorviqua
Experimental: PF-07284892 in combination with encorafenib and cetuximab (Part 2); Combination dose escalation of PF-07284892 in combination with encorafenib and cetuximab in participants with BRAF V600E mutant CRC	Drug: PF-07284892; PF-07284892; Other Names: ARRY-558; Biological: cetuximab; cetuximab; Other Names: Erbitux; Drug: encorafenib; encorafenib; Other Names: Braftovi, PF-07263896, LGX818
Experimental: PF-07284892 in combination with binimetinib (Part 2); Combination dose escalation of PF-07284892 in combination with binimetinib in participants with Ras-mutant, NF-1 mutant or BRAF class 3 -mutant solid tumors	Drug: PF-07284892; PF-07284892; Other Names: ARRY-558; Drug: binimetinib; binimetinib; Other Names: Mektovi, PF-06811462, MEK162
Experimental: Expansion Phase (Cohort 1); PF-07284892 + lorlatinib in participants with ALK+ NSCLC with prior lorlatinib	Drug: PF-07284892; PF-07284892; Other Names: ARRY-558; Drug: lorlatinib; lorlatinib; Other Names: Lorbrena; PF-06463922, Lorviqua
Experimental: Expansion Phase (Cohort 2); PF-07284892 + lorlatinib in participants with ALK+ NSCLC with no prior lorlatinib	Drug: PF-07284892; PF-07284892; Other Names: ARRY-558; Drug: lorlatinib; lorlatinib; Other Names: Lorbrena; PF-06463922, Lorviqua
Experimental: Expansion Phase (Cohort 3); PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with prior BRAF inhibitor (BRAFi) plus epidermal growth factor receptor inhibitor (EGFRi)	Drug: PF-07284892; PF-07284892; Other Names: ARRY-558; Biological: cetuximab; cetuximab; Other Names: Erbitux; Drug: encorafenib; encorafenib; Other Names: Braftovi, PF-07263896, LGX818
Experimental: Expansion Phase (Cohort 4); PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with no prior BRAFi plus EGFRi	Drug: PF-07284892; PF-07284892; Other Names: ARRY-558; Biological: cetuximab; cetuximab; Other Names: Erbitux; Drug: encorafenib; encorafenib; Other Names: Braftovi, PF-07263896, LGX818
Experimental: Expansion Phase (Cohort 5); PF-07284892 + binimetinib in participants with RAS- mutant, NF1-mutant or BRAF class 3 mutant solid tumors who have received prior standard of care (SOC)	Drug: PF-07284892; PF-07284892; Other Names: ARRY-558; Drug: binimetinib; binimetinib; Other Names: Mektovi, PF-06811462, MEK162

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and Part 2- Number of participants with dose limiting toxicities (DLTs)	DLTs will be evaluated during the first cycle (21 days) as both a single agent or in combination with lorlatinib, encorafenib + cetuximab, or binimetinib. The number of DLTs will be used to determine the maximum tolerated dose (MTD)/recommended dose for further study	Cycle 1 (21 days)
Part 1 and Part 2- Number of participants with treatment-emergent adverse events (AEs)	AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy	Baseline up to 30 days after last dose of study medication
Part 1 and Part 2 - Number of participants with clinically significant change from baseline in laboratory abnormalities	Laboratory abnormalities as characterized by type, frequency, severity, and timing	Baseline up to 30 days after last dose of study treatment
Part 1 and Part 2 - Number of dose interruptions, dose modifications, and discontinuations due to AEs	Incidence of dose interruptions, dose modifications, and discontinuations due to AEs	Baseline up to 30 days after the last dose of study medication
Part 3- Overall response	Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)	Baseline to up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and Part 2- Maximum plasma concentration (Cmax) of PF-07284892 and metabolite	single dose (Cmax) and multiple dose (assuming steady state is achieved; Css,max) pharmacokinetic (PK) parameters	Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8 hours postdose); Cycle 1 Day 18 (predose, 1, 2, 4, 6, 8, 24, and 48 hours postdose); Cycle 2-6 Day 1 (predose and 2 hours postdose); Cycle 7-12 Day 1 predose; end of treatment (EOT)
Part 1 and Part 2- Time to reach maximum plasma concentration (Tmax) of PF-07284892 and metabolite	Single dose (Tmax) and multiple dose (assuming steady state is achieved; Tss,max) pharmacokinetic parameters	Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8 hours postdose); Cycle 1 Day 18 (predose, 1, 2, 4, 6, 8, 24, and 48 hours postdose); Cycle 2-6 Day 1 (predose and 2 hours postdose); Cycle 7-12 Day 1 predose; EOT
Part 1 and Part 2- Area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) of PF-07284892 and metabolite	Single dose PK parameter	Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8 hours postdose); Cycle 1 Day 18 (predose, 1, 2, 4, 6, 8, 24, and 48 hours postdose); Cycle 2-6 Day 1 (predose and 2 hours postdose); Cycle 7-12 Day 1 predose; EOT
Part 1 and Part 2- Area under the plasma concentration-time curve from time 0 to extrapolated to infinity (AUCinf) of PF-07284892 and metabolite	Single dose and multiple dose (assuming steady state is achieved) PK parameter	Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8 hours postdose); Cycle 1 Day 18 (predose, 1, 2, 4, 6, 8, 24, and 48 hours postdose); Cycle 2-6 Day 1 (predose and 2 hours postdose); Cycle 7-12 Day 1 predose; EOT
Part 1 and Part 2- Metabolite ratio of PF-07284892 and metabolite	Single dose PK parameter	Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8 hours postdose); Cycle 1 Day 18 (predose, 1, 2, 4, 6, 8, 24, and 48 hours postdose); Cycle 2-6 Day 1 (predose and 2 hours postdose); Cycle 7-12 Day 1 predose; EOT
Part 1 and Part 2- Area under the plasma concentration-time curve from 0 to 24 (AUC24) or 48 hours (AUC48) of PF-07284892 and metabolite	Multiple dose (assuming steady state is achieved) PK parameter	Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8 hours postdose); Cycle 1 Day 18 (predose, 1, 2, 4, 6, 8, 24, and 48 hours postdose); Cycle 2-6 Day 1 (predose and 2 hours postdose); Cycle 7-12 Day 1 predose; EOT
Part 1 and Part 2- Overall response	Response will be evaluated via radiographical tumor assessments by RECIST v1.1	Baseline to up to 2 years
Part 2- Duration of Response (DOR)	Time from the first documentation of objective response to the first documentation of objective progressive disease, relapse or to death due to any cause	Baseline to up to 2 years

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2021
• Primary Completion (Estimated): June 4, 2024
• Study Completion (Estimated): November 29, 2025

Study Registration Dates

• First Submitted: March 9, 2021
• First Submitted That Met QC Criteria: March 13, 2021
• First Posted (Actual): March 16, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: colorectal cancer; non-small cell lung cancer; ROS1; B-type Raf proto-oncogene (BRAF) mutation; Ras mutation; anaplastic lymphoma kinase (ALK)-positive; neurofibromatosis type 1 (NF1)
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: C4481001; 2022-502431-18-00 (Registry Identifier: CTIS (EU)); 2022-003166-21 (EudraCT Number); SHP2 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No